Epidural hydroxyethyl starch ameliorating postdural puncture headache after accidental dural puncture : Chinese Medical Journal

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Original Article

Epidural hydroxyethyl starch ameliorating postdural puncture headache after accidental dural puncture

Zhou, Yin; Geng, Zhiyu; Song, Linlin; Wang, Dongxin

Editor(s): Yin, Yanjie

Author Information
Chinese Medical Journal ():10.1097/CM9.0000000000001967, January 3, 2023. | DOI: 10.1097/CM9.0000000000001967



Accidental dural puncture (ADP) remains the most common complication encountered during obstetric epidural anesthesia and analgesia.[1-4] The risk of subsequent postdural puncture headache (PDPH) is estimated to be between 76% and 85% after ADP with a 16 to 18-gauge needle.[5-7] Although PDPH is self-resolving in approximately 1 or 2 weeks in most obstetric patients with ADP, they may suffer from moderate to severe headaches that hinder them from taking care of themselves and their babies. Occasionally, significant morbidities associated with PDPH, including subdural hematoma, cerebral venous thrombosis, bacterial meningitis, persistent headache, or depression, may develop.[8-10] Severe headaches and expectant treatment of PDPH inevitably lead to discharge delay and increased healthcare costs.[11]

Preventing the development of PDPH when the dura is accidentally punctured by a large bore epidural needle is as important as treating it when it occurs. Various prophylactic modalities for PDPH have been investigated extensively for the management of recognized ADP with variable success. Currently, there are no convincing modalities that have been shown to offer complete prevention for headache after ADP during obstetric epidural procedures.[12-17] Invasive strategies, such as resited epidural catheters, intrathecal catheters, and epidural blood patch (EBP) have been demonstrated to be inconclusive with respect to preventing PDPH in previous investigations[18-20]

The existing literatures suggested that epidural hydroxyethyl starch (HES) is an alternative to EBP for short-term relief of PDPH after ADP when EBP is not feasible.[21,22] EBP is an invasive procedure. Patients with local/systemic infection and coagulopathy are contraindicated to EBP’ which are not infrequent in postpartum patients. Severe complications associated with EBP such as meningitis, subdural or intrathecal hematoma, arachnoiditis, cauda equina syndrome’ and permanent paraparesis’ have been published in case reports.[23-25] In contrast, epidural administration of HES via the re-sited epidural catheter is relatively simple and noninvasive, despite the off-label use and unclarified safety profiles. The great efficacy of this incorporated prophylactic strategy has been empirically observed in our clinical practice. Therefore, we undertook this retrospective study to evaluate the role of epidural administration of HES in headache prophylaxis following ADP during obstetric epidural procedures, regarding the prophylactic efficacy and side effects. We hypothesized that this incorporated prophylactic strategy would be associated with a reduced incidence of PDPH.


Ethical approval

The study procedures were in accordance with the Helsinki Declaration of 1975 (as revised in 2000) and approved by the Ethical Committee of Peking University First Hospital (2020-396). The individual consent for this retrospective analysis was waived.

The obstetric unit at our institution is a tertiary obstetric referral center with 6000 to 7000 deliveries annually. Up to 80% of parturients receive neuraxial anesthesia for their deliveries, either epidural analgesia for labor or epidural/combined spinal-epidural (CSE) anesthesia for cesarean deliveries. From 2019, as a service initiative, all recognized ADPs during epidural procedures were registered in a database by in-charge anesthesiologists, along with a description of clinical data, including the management for ADP and the outcomes. We reviewed the records of patients between January 2019 and February 2021 in the ADP database.

Anesthesia care for labor and cesarean delivery

For labor epidural analgesia, a 20-gauge epidural catheter is inserted with a 16-gauge Tuohy needle. Patient-controlled epidural analgesia is achieved with ropivacaine and sufentanil at a basal rate of 4 mL/h and a 6 mL demand bolus.

Cesarean delivery is performed under CSE anesthesia as the standard of care. A 16-gauge Tuohy needle is employed, and plain bupivacaine is administered via a 27-gauge Whitacre spinal needle to provide surgical anesthesia. A 20-gauge epidural catheter is inserted for postoperative analgesia. For cases under labor analgesia requiring cesarean delivery, epidural anesthesia via the epidural catheter in situ is routinely topped up with lidocaine or ropivacaine. After delivery, patients receive a continuous epidural infusion of ropivacaine and sufentanil at a rate of 5 mL/h for 48 h.

Definition of a recognized ADP

ADP is recognized by visualizing the free flow of cerebral spinal fluid (CSF) either via the Tuohy needle or via the epidural catheter or showing a high level of anesthesia upon administration of an epidural test dose.

PDPH prophylaxis after ADP

No universal management protocol for a recognized ADP exists at our institution. In the case of ADP, the epidural catheter was re-sited for anesthesia or analgesia, if possible. The patient was given a standard written document that describes the possibility of PDPH and the possible consequences associated with various prophylactic strategies after re-siting the epidural catheter [Supplementary File, https://links.lww.com/CM9/A915]. The patient has their sole discretion over what strategies are employed for PDPH prophylaxis. The prophylactic modalities employed at our institution are as follows: (1) Re-siting epidural catheter and epidural analgesia (Epidural-alone). In the case of witnessed ADP, epidural needles are usually withdrawn until CSF ceases to flow. Alternatively, a second puncture is performed at the same level or adjacent to that where the original dural puncture occurs. Subsequent epidural dosing and duration of catheter indwell are as per standard anesthesia care. The patient is freely ambulated postpartum. (2) Epidural HES on epidural analgesia (HES-Epidural). Epidural analgesia is maintained as per departmental routines. Thirty minutes following epidural analgesia, 15 mL of HES 6% 130/0.4 (Voluven, Fresenius Kabi, China) is slowly injected via an epidural catheter, as tolerated by the patient. The dosing timing is chosen to diminish the impact of epidural HES on the effectiveness of the analgesia. The patient is freely ambulated postpartum. (3) Two doses of epidural HES, respectively, on and after epidural analgesia (HES-Epidural-HES). Epidural analgesia is maintained as per departmental routines. Thirty minutes following epidural analgesia, 15 mL of HES is administered via the epidural catheter. The epidural catheter is placed in situ for 24 h after labor or 48 h after cesarean delivery, with the previous analgesic setting unchanged. At the end of epidural analgesia, another 10 to 15 mL of HES is injected into the epidural space before catheter removal, as tolerated by the patient. The patient is freely ambulated postpartum. (4) Accidental intrathecal catheter placement. In cases of accidental intrathecal catheterization, neuraxial analgesia and anesthesia are maintained with an intrathecal infusion of ropivacaine and sufentanil. (5) Conservative management. In the case that puncture difficulty is encountered, epidural placement is aborted. A combination of bed rest and oral or intravenous hydration is recommended.

PDPH identification and follow-up

The diagnosis of PDPH was made by the Department of Anesthesiology’ s acute pain service team. The definition is based on the International Classification of Headache Disorders-3 criteria.[26] PDPH is a headache that develops within 5 days of dural puncture, worsens when attaining an upright position, and is relieved after resuming a recumbent position, with at least one accompanying symptom, such as stiffness of the neck and shoulders, tinnitus, hypacusia, vertigo, diplopia, photophobia, phonophobia, or nausea/vomiting. Maximum headache pain severity was rated on a 0 to 10 numeric rating scale (0 = no pain, 10 = worst imaginable pain; mild 1 to 3, moderate 4 to 7, and severe 8 to 10). All patients who experienced a recognized ADP were visited approximately between 8 AM and 12 am daily by the acute pain service team to enquire about the presence and/or the severity of headache during their hospital stay and were contacted by telephone once a week if the patient was discharged until 1 month after the ADP. For the patients who sustained headache after discharge, they were instructed to record the severity of headache by means of a headache diary. Patients were also informed of the team’ s contact information and instructed to actively report adverse events including paresthesias and motor deficits by telephone beyond the follow-up period.

Treatment of PDPH

Patients with mild and moderate headache are typically initiated with conservative management, including bed rest, hydration, caffeine intake, and oral analgesics (paracetamol, nonsteroidal anti-inflammatory agents, and tramadol). For patients experiencing severe headache, EBP or HES is recommended for the treatment of PDPH.

ADP database

The ADP database is a smartphone application, which can be accessed by scanning a quick response code within the working area. The anesthesiologists and acute pain service team follow the service initiative’ s requirements to finish entering the database, once an ADP is encountered. The incharge anesthesiologists fill out the prespecified items regarding the patients’ information, puncture details, and prophylactic strategies taken in the registration interface of the application. The acute pain service team, who is not involved in anesthesia procedures and the registration interface of the application, is alerted to the patients’ identifier codes and locations by the application, when the patients are registered in the database. The team follows up the patients and enters data in the follow-up interface of the application. No missing data are allowed during the filling process by the application. For this retrospective study, the data of the registered patients were extracted from the database by one investigator.

Outcome measures

Data collected included baseline demographics, obstetric information, anesthetic technique, mode of ADP, prophylactic strategies, the presence of PDPH, onset, severity and duration of headache, type of treatment, and duration of hospital stay postpartum. Side effects potentially associated with prophylactic strategies, including back pain, paresthesias, and neurologic deficits, were recorded.

The primary outcome was the presence of PDPH. No subgroup or sensitivity analyses were identified. The clinically meaningful effect size was defined a priori as a 40% reduction in the rate of PDPH, based on the previous reports of a PDPH rate following ADP of 76% to 85%.[5-7] Secondary outcomes examined included onset, severity and duration of headache, adverse effects related to prophylactic strategies, and discharge delay because of PDPH. As per the standard of care at our institution, the hospital length of stay after delivery is 3 days after cesarean delivery and 2 days after labor. The duration of hospital discharge delay that was because of PDPH was defined as the number of days when the patient remained in the hospital for the treatment of PDPH symptoms, although discharge criteria were met as per the obstetric team.

Statistical analysis

Descriptive statistics are presented as the mean ± standard deviation, median (interquartile range), or counts and percentages where appropriate. Continuous data were assessed for normality of distribution using histograms and the Kolmogorov–Smirnov test. One-way analysis of variance was used for comparisons across the three groups when the variables were normally distributed.

The Kruskal–Wallis H test was used for three-group comparisons of nonnormally distributed continuous variables with Bonferroni correction (α = 0.05/3). Pearson chi-squared or Fisher exact test was used to comparing categorical data.

Univariable logistic regression was used to compare demographic, obstetric, and anesthetic characteristics of patients with and without PDPH, with a predefined P < 0.05. Identified variables from these analyses were retained as covariates for the subsequent multivariable logistic regression model. The odds ratios (ORs) for PDPH and 95% confidence intervals (CIs) were calculated. All tests were performed two-sided, with P < 0.05 considered statistically significant (except for the univariable analysis for potential risk factors for PDPH). Statistical analysis was performed using SPSS version 24.0 Software (IBM, Armonk, NY, USA).


Prophylactic strategies for patients experiencing ADP

Over the study period, a total of 11,546 obstetric patients received epidural procedures for labor or cesarean delivery. Figure 1 presents the study flow diagram. One hundred and twelve patients were identified as having a recognized ADP, yielding an incidence of 0.97%. Of these patients, 108 experienced ADP during epidural placement, while four patients accidentally had an intrathecal catheter placed, which was left in situ and successfully used for subsequent anesthesia or analgesia. Of the 108 experiencing ADP during epidural procedures, three had difficulty with re-siting an epidural catheter or unsuccessful epidural blocks, and epidural procedures were aborted.

Figure 1:
Study flow diagram. ADP: Accidental dural puncture; HES: Hydroxyethyl starch; PDPH: Postdural puncture headache.

Of the remaining 105 ADP patients, 46 patients solely had a re-sited epidural catheter placed with epidural analgesia, 25 were administered epidural HES shortly after establishing epidural analgesia, and 34 received two doses of epidural HES, respectively, on and after epidural analgesia. Re-sited epidural catheters were successfully used in all of these patients. Five patients agreed to receive the HES-Epidural-HES strategy but had their catheters completely dislodged ahead of standard protocols, which were later included in the HES-Epidural patients in the analysis. Another six patients receiving Epidural-alone and three receiving HES-Epidural had their epidural catheters completely dislodged ahead of the scheduled catheter withdrawal, all of which were included in the analysis.

PDPH characteristics with various prophylactic strategies

No significant differences were detected among the patients with the Epidural-alone, HES-Epidural, and HES-Epidural-HES strategies regarding patient characteristics [Table 1]. Of the 105 patients with a re-sited epidural catheter for PDPH prophylaxis, 46 (43.8%) developed PDPH. The duration of headache lasted for a median of 7 (4.8–8.0) days, with onset at a median of 30 (20–36) h for all patients. The headache was typically occipital/frontal in location, with 26.1% of patients reporting severe headache during the course of PDPH. A discharge delay that was because of PDPH was observed in 13% of headache patients.

Table 1 - Patient characteristics and clinical data based on prophylactic strategies with a re-sited epidural catheter.
Characteristics Epidural analgesia alone (n = 46) HES-Epidural analgesia (n = 25) HES-Epidural analgesia-HES (n = 34) P value
Age (years) 34 ± 4 35± 4 33± 4 0.395
Nulliparous 24 (52.1) 9 (36.0) 19 (55.9) 0.300
BMI (kg/m2) 28.3 ± 3.6 27.2 ± 3.5 26.8 ± 4.8 0.258
Gestational age (weeks) 39 ± 3 39± 2 39± 2 0.616
Preexisting headache 4 (8.7) 1 (4.0) 2 (5.9) 0.888
Preeclampsia 2 (4.3) 1 (4.4) 2 (5.9) 1.000
Anesthetic technique 0.968
 Epidural analgesia 23 (50.0) 13 (52.0) 18 (52.9)
 CSE anesthesia 23 (50.0) 12 (48.0) 16 (47.1)
Mode of delivery 0.505
 Normal vaginal delivery 14 (30.4) 9 (36.0) 14 (41.2)
 Instrumental vaginal delivery 3 (6.5) 2 (8.0) 5 (14.7)
 Cesarean delivery 29 (63.1) 14 (56.0) 15 (44.1)
Duration of epidural infusion (h) 28 (10–48) 27 (7–48) 34 (27–48) 0.158
Volume of epidural infusion (mL) 145 (67–250) 140 (56-250) 195 (135–240) 0.111
Volume of epidural HES (mL) 15 (15–15) 30 (30–30) <0.001
Data are shown as n (%), mean ± standard deviation or median (interquartile range). P < 0.017 for group comparison with Bonferroni correction. BMI: Body mass index; CSE: Combined spinal-epidural; HES: Hydroxyethyl starch.

The PDPH characteristics among patients with the strategies with a re-sited epidural catheter are summarized in Table 2. For the primary outcome, a significant difference was seen in the incidence of PDPH across the patients receiving Epidural-alone, HES-Epidural, and HES-Epidural-HES, with progressively lower proportions of PDPH patients observed (Epidural-alone, 31/46 [67.4%], HES-Epidural 10/25 [40.0%], and HES-Epidural-HES 5/34 [14.7%]; difference in frequency [95% CI] for HES-Epidural-HES vs. Epidural-alone and HES-Epidural, 52.7% [31.6–67.0] and 25.3% [2.6–46.3], respectively; P < 0.001). Late-onset (after catheter removal) of PDPH was more frequent in the patients receiving Epidural-alone and HES-Epidural compared with the HES-Epidural-HES patients (P = 0.014). Patients with the HES-Epidural and HES-Epidural-HES strategies experienced a shorter length of symptoms than those receiving Epidural-alone, although the differences did not reach a significant level with Bonferroni correction (P = 0.037 and 0.019, respectively).

Table 2 - PDPH characteristics based on prophylactic strategies with a re-sited epidural catheter.
Characteristics Epidural analgesia alone (n = 46) HES-Epidural analgesia (n = 25) HES-Epidural analgesia-HES (n = 34) P value
PDPH 31 (67.4) 10 (40.0) 5 (14.7) <0.001
Reported headache severity
 Mild 9 (29.0) 2 3 0.416
 Moderate 12 (38.7) 6 2
 Severe 10 (32.3) 2 0
Maximum headache NRS (0–10) 6 (3–8) 6 (4–7) 3 (2–3) 0.155
Headache onset after ADP (h) 30 (20–36) 34 (20–38) 27 (26–32) 0.338
Headache onset timing
 Prior to catheter removal 6 (19.4) 4 4 0.014
 After catheter removal 25 (80.6) 6 1
Headache duration (days) 7.0 (5.0–9.0) 5.3 (2.0–7.3) 4.2 (2.0–5.0) 0.027
Neck stiffness 15 (48.4) 6 2 0.816
Shoulder stiffness 10 (32.3) 4 0 0.345
Nausea/vomiting 5 (16.1) 2 0 1.000
Diplopia 1 (3.2) 0 0 1.000
Photophobia 1 (3.2) 0 0 1.000
Hypacusia 1 (3.2) 0 0 1.000
Type of treatment
 Number of oral analgesics 2 (1–3) 2 (2–2) 1 (0–1) 0.418
 EBP 0 0 0 1.000
Hospital length of stay postpartum (h) 77 (70–93) 83 (70–115) 72 (66–89) 0.274
Discharge delay that was because of headache 5 (16.1) 1 0 1.000
Data are shown as n, n (%) or median (interquartile range). P < 0.017 for group comparison with Bonferroni correction. n (% PDPH patients). ADP: Accidental dural puncture; EBP: Epidural blood patch; HES: Hydroxyethyl starch; NRS: Numeric rating scale; PDPH: Postdural puncture headache.

Adverse events associated with various prophylactic strategies

No neurologic deficits, including paresthesias and motor deficits, related to prophylactic strategies used in any patient were detected by the team or actively reported by the patients from at least 2 months to up to >2 years after delivery. Two patients receiving HES-Epidural and four receiving HES-Epidural-HES reported backache during epidural administration of HES, yielding an overall backache rate related to HES administration of 10%. One patient with HES-Epidural-HES (1.7% [1/59] of those receiving epidural HES) complained of transient headache when receiving the second dose of HES, which resolved quickly after suspending the administration.

Risk factors for PDPH

Univariable analyses revealed that there were significant differences between the PDPH and non-PDPH patients with respect to the prophylactic strategies (P < 0.05) [Table 3]. In the multivariable regression analysis, the HES-Epidural-HES strategy was significantly associated with a decrease in PDPH development, in contrast to resiting an epidural catheter alone (OR 0.030, 95% CI 0.006–0.143; P < 0.001).

Table 3 - Comparison of patient characteristics and clinical data between the PDPH and non-PDPH patients with a re-sited epidural catheter.
Characteristics Non-PDPH (n = 59) PDPH (n = 46) Difference in mean, median, or proportions (95% CI) P value
Age (years) 34 ± 4 33± 4 1 (−1 to 3) 0.235
Nulliparous 31 (52.5) 21 (45.7) 8.6 (−10.4 to 26.7) 1.000
BMI (kg/m2) 27.8 ± 4.2 27.1 ± 3.5 0.7 (−0.8 to 2.3) 0.363
Gestational age (week) 38 ± 3 38± 4 0 (−1 to 2) 0.625
Preexisting headache 3 (5.1) 4 (8.7) −3.6 (−13.9 to 8.5) 0.696
Preeclampsia 3 (5.1) 2 (4.3) 0.7 (−10.0 to 10.0) 1.000
Mode of delivery 0.767
 Normal vaginal delivery 19 (32.2) 18 (39.1) −6.9 (−24.6 to 11.0)
 Instrumental vaginal delivery 6 (10.2) 4 (8.7) 1.5 (−11.4 to 13.0)
 Cesarean delivery 34 (57.6) 24 (52.2) 5.5 (−13.2 to 23.8)
Initial intervertebral level 0.253
 L2–L3 31 (52.5) 19 (41.3) 11.2 (−7.8 to 29.1)
 L3–L4 28 (47.5) 27 (58.7) −11.2 (−30.2–6.7)
Prophylactic strategies <0.001
 Epidural analgesia alone 15 (25.4) 31 (67.4) −42.0 (−61.0 to −27.0)
 HES-Epidural analgesia 15 (25.4) 10 (21.7) 3.7 (−13.0 to 19.3)
 HES-Epidural analgesia-HES 29 (49.2) 5 (10.9) 38.3 (21.0–52.1)
P < 0.05 for univariable logistic regression analysis. BMI: Body mass index; CI: Confidence interval; HES: Hydroxyethyl starch; PDPH: Postdural puncture headache.

Epidural blood patch

All patients with ADP refused to receive EBP for prophylaxis or treatment of PDPH, because they had suffered remitting pain, or were concerned about the second dural puncture and/or the potential severe risk of infection and subdural/intrathecal hematoma.


This study suggested that the incorporated prophylactic strategy of continuous epidural analgesia combined with two doses of epidural HES, respectively, on and after epidural analgesia was associated with a significant decrease in the incidence of PDPH following ADP, compared with the strategies of epidural analgesia alone and HES on epidural analgesia.

It has been hypothesized that PDPH arises from persistent CSF leakage which leads to mechanical tension on pain-sensitive intracranial structures, or compensatory vasodilation.[27] We postulate that combining the positive effect of two prophylactic measures—epidural analgesia and epidural HES—into a single strategy would result in an additive and extended effect in reducing PDPH following ADP, which was evidenced by a reduced incidence of PDPH in the patients receiving the HES-Epidural-HES strategy.

It can be speculated that epidural administration of colloids increases pressure in the epidural space that limits CSF leakage, and induces a mass effect that causes a cephalad shift of CSF in the spinal compartment. Epidural injection of HES and gelatin were described as an alternative to an EBP to alleviate severe headache after ADP in several case reports.[21,22,28,29] Our study was underpowered to show the prophylactic efficacy of the HES-Epidural strategy. We speculate that the effect ofHES was relatively short-lived lasting approximately 24 h (but potentially much longer than saline), providing only a temporary increase in epidural pressure. The second dose of epidural HES immediately before catheter removal seemed to help prevent late-onset (after catheter removal) PDPH, as showed by our results in Table 2.

Previous randomized controlled trials demonstrated that prophylactic EBP given just before catheter removal did not have a significant effect on reducing PDPH following ADP during obstetric epidural procedures.[18,20] Prophylactic EBP was usually administered after resolution of analgesia/anesthesia, indicating a relatively short epidural catheter indwell time. Our patients receiving HES-Epidural-HES had their epidural catheters in situ for at least 24 h after delivery (except for those with unexpected catheter dislodgement). Enlightened by our results, maintaining an epidural catheter for at least 24 h followed by EBP might show improved prophylactic efficacy.

The advantages of epidural HES over EBP lie in its noninvasiveness, ease in use, and less potential for infectious complications. In addition, epidural administration of HES can be repeated as needed via an in situ epidural catheter without the need for another dural puncture, which is usually impossible for EBP, because the blood clot injected blocks the epidural catheter easily and prohibits further use of the catheter.

The reported efficacy of re-sited epidural catheters in studies is variable.[12,30-32] The incidence of PDPH with Epidural-alone (67.4%) was similar to those reported in previous studies.[30,33] The supposed mechanism of a potential protective role of a re-siting epidural catheter might be increasing epidural pressure through epidural infusion or repeat epidural boluses, and/or mechanically blocking the newly created dural hole.[12] The effect of epidural saline administration, however, is usually transient. As mirrored by the results of the patients receiving Epidural-alone, the onset of headache was after catheter removal in 80.6% of symptomatic patients. Another concern related to re-siting an epidural catheter with continuous epidural analgesia is unexpected partial/complete catheter dislodgement, because of fluid extravasation causing wet dressing and subsequent loose fixation. Unexpected complete catheter dislodgement was observed in 13.3% of our patients with re-siting epidural catheters. Partial catheter dislodgement may not be unusual as well. The short indwell time might have a negative impact on the efficacy of the re-siting of an epidural catheter. Meticulous catheter fixation and care is a prerequisite for efficacious prophylactic strategies to be administered.

Safety data on the use of epidural HES are lacking. The reported adverse events in our patients receiving epidural HES were mainly mild back pain or headache, potentially originating from a mass effect on neurological tissue within the epidural space, with the incidence being comparable to that caused by EBP.[19] Experimental studies indicated that HES has a positive role in improving microcirculation and attenuating inflammation.[34,35] A previous rat and sheep study reported that with HES (450 kD) infusion, HES storage vacuoles were typically detectable in macrophages of small peripheral nerves in the skin, liver, lung, and kidney, and were not associated with signs of either inflammation or apoptosis.[36] Deposits of HES could be detected in perineural and endoneural cells of sciatic nerve. A study evaluating pruritus following various cumulative dosages of HES infusion in 93 patients revealed that dose-dependent HES-reactive vacuoles could be demonstrated in the Schwann cells of unmyelinated, as well as small myelinated, nerve fibers, and endoneural and perineural cells in the skin.[37] Subsequent neural devacuolization indicated regular metabolism of HES within 3 years. High molecule weight HES (450 kD) has been suggested to be harmful to the kidney, coagulation, and reticuloendothelial system, possibly related to their retention in vulnerable cells.[38,39] The modern generation is supposed to be free of these toxic effects because of their low molecular weight and degree of substitution. A case series reported two patients who received epidural HES for PDPH treatment when an EBP was contraindicated.[21] Relief of headache was achieved with no adverse effects. In a study evaluating epidural volume extension using colloids in combined spinal–epidural anesthesia for cesarean delivery, 33 pregnant patients received epidural 6% HES 200/0.5 and did not report any neurologic deficits postoperatively.[40] Two case series on the utility of epidural HES mostly for PDPH prophylaxis after obstetric ADP including 8 and 20 patients, respectively, reported that no serious adverse effects such as neurological deficits were detected.[22,41] Two recent rat studies indicated that single or repeated intrathecal injection of HES did not induce any clinical or histopathological evidence of long-term neuronal toxicity.[42,43] Although no adverse events potentially associated with epidural HES were reported, safety evidence should be sought further in this circumstance.


This study had a limited sample size and was undertaken at a single obstetric center, which limited the generalizability of the results reported in our study to other circumstances. Our study was likely underpowered to address adequately some secondary outcomes such as headache severity, delayed discharge, and serious neurological deficits potentially related to prophylactic strategies. This study is also subject to the selection bias inherent in retrospective studies, given the decision to employ which strategy was made by the parturients themselves. We acknowledge that confounding variables might have an impact on our findings because neither patients nor investigators were blinded to the prophylactic strategies. The present study is hypothesis-generating, and conducting a prospective trial would be optimal to evaluate the efficacy and safety of this incorporated prophylactic strategy for PDPH.


Our findings suggested that the incorporated prophylactic strategy employed in our study was associated with a great decrease in the risk of PDPH following ADP during obstetric epidural procedures. This strategy consisted of re-siting an epidural catheter with continuous epidural analgesia and two doses of epidural HES on and after epidural analgesia, respectively. Prospective, randomized, and double-blinded trials are required before prophylactic HES administration can be recommended.

Conflicts of interest



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Accidental dural puncture; Epidural analgesia; Hydroxyethyl starch; Postdural puncture headache; Prophylaxis

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